Rationale for selection of animal species and sex for preclinical studies MCQs With Answer

Introduction

The rationale for selection of animal species and sex in preclinical studies guides reliable toxicology and pharmacology data generation for B. Pharm students. Key considerations include physiological similarity to humans, pharmacokinetics, metabolic enzymes, reproductive status, strain differences, route of administration, and regulatory guidelines (ICH, OECD). Ethical principles and the 3Rs (Replacement, Reduction, Refinement) also shape species and sex choices. Understanding species-specific ADME, disease models, dose scaling, and sex-related variability improves translational relevance and safety assessment. Mastery of these concepts helps design robust studies, interpret interspecies differences, and meet regulatory expectations. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which primary factor most influences the choice of an animal species for systemic pharmacokinetic studies?

• Cost of the animal
• Similarity of metabolic enzymes and ADME to humans
• Availability of animal housing
• Ease of blood sampling

Correct Answer: Similarity of metabolic enzymes and ADME to humans

Q2. For regulatory chronic toxicity studies, guidelines commonly require at least one non-rodent species because:

• Non-rodents are cheaper to maintain
• Rodents cannot metabolize drugs
• Non-rodents may better predict human responses for certain endpoints
• Ethical rules mandate more species

Correct Answer: Non-rodents may better predict human responses for certain endpoints

Q3. Which species is often chosen as the non-rodent in preclinical safety studies due to similar skin and cardiovascular physiology to humans?

• Mouse
• Rabbit
• Dog
• Miniature pig

Correct Answer: Miniature pig

Q4. Sex selection in preclinical studies is important because:

• Males are always more sensitive to drugs
• Females are easier to handle
• Sex-related hormonal differences can alter pharmacokinetics and toxicity
• Only males are required by guidelines

Correct Answer: Sex-related hormonal differences can alter pharmacokinetics and toxicity

Q5. The 3Rs principle influences species choice by promoting:

• Replacement of animals with humans
• Reduction of sample sizes without statistical consideration
• Replacement, Reduction, and Refinement to minimize animal use and suffering
• Refusal to conduct any animal testing

Correct Answer: Replacement, Reduction, and Refinement to minimize animal use and suffering

Q6. Which regulatory guideline specifically addresses safety pharmacology and selection of species for core battery tests?

• ICH M3
• OECD 420
• ICH S7A/S7B
• FDA GCP

Correct Answer: ICH S7A/S7B

Q7. Allometric scaling is used in species selection to:

• Convert dose based on cost-effectiveness
• Predict human pharmacokinetic parameters from animal data using body size and physiology
• Determine the ease of breeding animals
• Avoid performing toxicology studies

Correct Answer: Predict human pharmacokinetic parameters from animal data using body size and physiology

Q8. Which rodent is most commonly used for mechanistic toxicology and genetic models?

• Rabbit
• Rat
• Mouse
• Ferret

Correct Answer: Mouse

Q9. When investigating reproductive toxicity, why might one include both sexes and mating studies?

• To increase overall animal numbers only
• Because reproductive toxicity affects fertility, embryonic development, and parental functions in both sexes
• Males are not relevant to reproductive safety
• Females provide all necessary data

Correct Answer: Because reproductive toxicity affects fertility, embryonic development, and parental functions in both sexes

Q10. Which factor argues for using an inbred strain versus outbred strain in preclinical studies?

• Inbred strains provide genetic uniformity to reduce variability in mechanistic studies
• Outbred strains are genetically identical
• Inbred strains cost less
• Outbred strains are unethical

Correct Answer: Inbred strains provide genetic uniformity to reduce variability in mechanistic studies

Q11. A drug metabolized predominantly by CYP3A in humans should be tested in a species where:

• CYP3A is absent
• CYP3A expression and activity are similar to humans
• Only glucuronidation occurs
• Metabolism is irrelevant

Correct Answer: CYP3A expression and activity are similar to humans

Q12. Which species is often chosen for embryofetal development studies because of similarities in placentation and gestational physiology?

• Dog
• Sheep
• Rabbit
• Non-human primate

Correct Answer: Non-human primate

Q13. When might a single-sex study be justified in preclinical testing?

• When the drug target is sex-specific or early data show no sex-related differences and regulators agree
• When researchers prefer one sex
• Species selection is unclear
• It is never justified

Correct Answer: When the drug target is sex-specific or early data show no sex-related differences and regulators agree

Q14. Which consideration is critical when selecting the rabbit for developmental toxicity studies?

• Rabbits have a very long lifespan
• Rabbits are resistant to all teratogens
• Rabbits can be sensitive to maternal toxicity and have different placental transfer characteristics
• Rabbits metabolize drugs identically to humans

Correct Answer: Rabbits can be sensitive to maternal toxicity and have different placental transfer characteristics

Q15. In immunotoxicity assessments, why might non-rodent species be required?

• Because rodent immune systems always match humans
• To evaluate immune endpoints when rodent responses do not predict human immune reactions
• Non-rodents are cheaper
• Regulators prefer larger animals regardless of data

Correct Answer: To evaluate immune endpoints when rodent responses do not predict human immune reactions

Q16. The estrous cycle can confound pharmacology results in female rodents because:

• Hormonal fluctuations alter drug pharmacodynamics and pharmacokinetics
• Females are always resistant to drugs
• Cycling only affects behavior, not drug response
• Male hormones are more variable

Correct Answer: Hormonal fluctuations alter drug pharmacodynamics and pharmacokinetics

Q17. Which species is commonly used for inhalation toxicity due to similar airway anatomy and breathing patterns to humans?

• Mouse
• Rat
• Dog
• Non-human primate

Correct Answer: Non-human primate

Q18. Selecting juvenile animals is necessary when:

• The intended human population includes pediatric patients and developmental differences affect safety and dosing
• The drug is only for elderly patients
• Juveniles are cheaper
• Pediatric use is not anticipated

Correct Answer: The intended human population includes pediatric patients and developmental differences affect safety and dosing

Q19. Which is a practical reason to select rats over mice for toxicology studies?

• Rats have smaller blood volume making sampling harder
• Rats are less characterized genetically
• Rats provide larger blood volumes for repeated sampling and established historical control data
• Mice are always preferred for toxicology

Correct Answer: Rats provide larger blood volumes for repeated sampling and established historical control data

Q20. When a biologic therapeutic binds a human-specific target, the preferred preclinical option is:

• Standard rodent models without modification
• In vitro testing only
• Use of species or transgenic models expressing the human target or non-human primates if cross-reactive
• Skipping preclinical studies

Correct Answer: Use of species or transgenic models expressing the human target or non-human primates if cross-reactive

Q21. Which endpoint often necessitates selecting a species with similar cardiovascular physiology to humans?

• Dermal irritation
• QT interval and arrhythmia risk assessment
• Fecal output
• Fur color changes

Correct Answer: QT interval and arrhythmia risk assessment

Q22. For topical dermatology products, species selection focuses on:

• Ability to vocalize discomfort
• Skin structure, thickness, absorption, and local tolerance comparability to humans
• Reproductive lifespan only
• Cardiac output exclusively

Correct Answer: Skin structure, thickness, absorption, and local tolerance comparability to humans

Q23. Which aspect of study design helps reduce the number of animals required while preserving statistical power?

• Ignoring variability
• Careful power calculation, appropriate controls, and use of crossover or repeated-measures designs when valid
• Using only males to halve the group size
• Random sampling without planning

Correct Answer: Careful power calculation, appropriate controls, and use of crossover or repeated-measures designs when valid

Q24. Which attribute of non-human primates often makes them the species of choice despite high cost and ethical concerns?

• High fecundity
• Close genetic and immunological similarity to humans for translation of complex biologics
• Lower regulatory scrutiny
• Rapid lifecycle

Correct Answer: Close genetic and immunological similarity to humans for translation of complex biologics

Q25. When a drug produces sex-specific adverse effects in early screens, the study strategy should include:

• Excluding the affected sex from further testing
• Detailed evaluation in both sexes with mechanistic studies to understand the basis of sex differences
• Assuming humans will not show the effect
• Only testing in one age group

Correct Answer: Detailed evaluation in both sexes with mechanistic studies to understand the basis of sex differences

Q26. Which is a limitation of using rodents to predict human drug metabolism?

• Rodents have identical enzyme expression to humans
• Species-specific differences in cytochrome P450 isoforms and conjugation pathways can alter metabolite profiles
• Rodents are too large
• Rodents do not show toxic effects

Correct Answer: Species-specific differences in cytochrome P450 isoforms and conjugation pathways can alter metabolite profiles

Q27. Which consideration is most relevant when choosing animals for dermal absorption studies of transdermal drugs?

• Fur density, stratum corneum thickness, and skin lipid composition
• Only the animal’s age
• Color of the skin
• Dietary preferences

Correct Answer: Fur density, stratum corneum thickness, and skin lipid composition

Q28. If a compound shows severe hepatotoxicity in one species but not others, the appropriate next step is to:

• Ignore the finding and proceed to humans
• Investigate species-specific mechanisms, compare metabolite profiles, and consult regulatory expectations before deciding
• Immediately stop all testing permanently
• Only test in smaller animals

Correct Answer: Investigate species-specific mechanisms, compare metabolite profiles, and consult regulatory expectations before deciding

Q29. In selection of species for inhalation studies, an important physiological parameter is:

• Ocular color
• Respiratory minute volume and nasal anatomy affecting deposition
• Tail length
• Incisor growth rate

Correct Answer: Respiratory minute volume and nasal anatomy affecting deposition

Q30. Which strategy improves translational relevance when early ADME data show major interspecies differences?

• Proceed to clinical trials without change
• Use physiologically based pharmacokinetic (PBPK) modeling, select alternative species or humanized models, and generate mechanistic data
• Ignore ADME differences
• Increase the dose in animals to match human exposure

Correct Answer: Use physiologically based pharmacokinetic (PBPK) modeling, select alternative species or humanized models, and generate mechanistic data

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com